Kaposi' sarcoma (KS) is a vascular neoplasm associated with HIV infection and often manifests in the oral cavity. Infection of Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV8), has been well established as the etiology of KS in the past decade. It has been shown that HIV infection modulates other viral infections via either direct HIV-virus interactions or alterations of host factors, including the immune system and cytokines. Several studies have also demonstrated KSHV infection and shedding in the oral cavity of HIV-infected subjects. The long-term goal of our research program is to understand the molecular mechanism of KSHV-induced pathogenesis, providing a scientific basis for preventive and therapeutic purposes. The objectiveof this application is to examine the molecular basis of interactions between HIV and KSHV in the oropharyngeal environments in order to test the central hypothesis that HIV infection alters oral environments, and as a result, modulates KSHV infection, latency and reactivation in the oral cavity. Two specific aims will be pursued: 1) To examine the modulation of KSHV viral loads and genotypes by HIV infection in the oral cavity; and 2) To examine the modulation of KSHV latency and reactivation by HIV infection in the oral cavity. We have established an extensive track record in KSHV research, and have already developed various technologies and related reagents that are needed for this project. The proposed study is significant because it will define the biology and virology of HIV-KSHV interactions in the oral cavity, and potentially identify novel therapeutic targets.